Both Gram-positive and Gram-negative pathogenic bacteria are causing significant health problems around the world due to these bacteria developing, or innately presenting, biochemical mechanisms that thwart medical management by various types of antibiotics. Effective use of pencillins, one major class of antibiotics, is particularly being threatened. For examples, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) has become resistant to control by penicillins, and Pseudomonas aeruginosa, an opportunistic member of Gram-negative bacteria, is innately beyond control of penicillins.
One area of concern is hospital-acquired or nosocomial parenteral antibiotic-resistant bacterial infections from topical colonized bacteria or suppurating infections. These types of bacteria frequently escape sterilization efforts prior to invasive procedures allowing them to enter the body and establish infection.
The acquiring of penicillin resistance by bacteria is life-threatening and is being addressed by the pharmaceutical industry through the development of new generations of penicillins. The pharmaceutical industry largely directs its efforts to creating new molecular alterations of existing penicillins in order to circumvent continually evolving resistance that in turn defeats efficacy of such new penicillins. Each generation of penicillins successively targets penicillin-resistant mechanisms in the bacterial coat in a way designed to circumvent biochemical resistance mechanisms that have evolved within pathogenic bacteria to resist previous generations of penicillins. It is unlikely that this cycle of new biochemical specificity for penicillin activity, followed by evolving resistance to that specificity, will be therapeutically successful since the percentages of penicillin-resistant pathogenic variants that defeat antibiotic management is rapidly increasing.
Penicillins bind to penicillin-binding proteins (PBPs) in the bacterial coat, and especially in Gram-positive bacteria those targets tend to evolve into non-binding or non-accessible motifs where, for example, one binding motif is said to be a 4-amino acid sequence -serine-X-X-lysine- that provides covalent acylation of serine by the beta-lactam ring of penicillins. In Gram-negative bacteria, resistance to penicillins is additionally complicated by the presence of transporters in the coat-associated outer membrane that export the influx of penicillin, and by similarly located porins that can restrict uptake of penicillin. Therefore, it is important to resolve both the evolved resistance to binding of penicillin to amino acid target motifs and the blockage of uptake of penicillin into cells, which together largely account for observed antibiotic resistance.
It is known that covalent binding of penicillins to PBPs of actively replicating bacterial cells leads to defective coats, which ultimately cause cell lysis and death. It is known that this covalent binding is commonly defeated by evolution of structural alteration in PBPs during development of penicillin resistance.
In addition, penicillin transport mechanisms also require proteins of specific structure to perform the function of penicillin efflux. Structural alterations of these proteins by pH, salt concentration, or dehydration are often reversible. For example, for at least one strain of MRSA, penicillin resistance is observed at pH 7.4; however, penicillin sensitivity is returned when those bacteria are exposed to penicillin at pH 5.6. Conversely to physico-chemically induced reversible denaturation, covalent binding of penicillin to PBP targets is not reversible, but rather immutable whether achieved in growing or static bacterial cells.
It is desirable to have a system and method for killing topical bacteria known to be penicillin-resistant, particularly MRSA and Pseudomonas aeruginosa. 
It is desirable to have a system and method for reversing the levels of penicillin-resistant bacterial infections that plague individuals in both community and hospital settings.
It is desirable to have a system and method for managing penicillin-resistance by mechanisms other than biochemical advances in the structure and/or activity of penicillin.
It is further desirable to have a system and method for altering in situ targets and inaccessibility of penicillin in bacteria by physico-chemical treatments, providing novel paradigms for effective topical applications of antibiotics and other drugs and antitoxins.